DESCRIPTION: (Applicant's Description) The major goal of this project is to determine the extent to which proton beams can decrease the damage to normal tissues that is often seen with standard photon treatments. It is our expectation that treatment morbidity will be decreased without a decrease in local control. The proposed clinical trials will be carried out for a variety of solid tumors where conventional photon treatments have provided suboptimal treatment outcomes. This work will be accomplished through the mechanism of Phase II/III clinical trials. We will assess clinical gains in terms of the incidence and severity of treatment-related acute and late effects of proton therapy compared to those for photon therapy. In addition, we will assess quality-of-life (QOL) in selected clinical trials. The higher proton beam energy, isocentric gantries, and increased treatment capacity at the Northeast Proton Therapy Center make it possible to safely deliver treatments to pediatric patients and to treat large numbers of patients in order to carry out expanded clinical trials. The proposed clinical trials are based on the rationale that proton beam treatments decrease the volume of normal tissues/organs receiving high doses of radiation, thereby decreasing the rate of treatment-related morbidity seen in photon therapy. This is particularity important in pediatric patients where the irradiated tissues and organs are immature and more sensitive to radiation damage. We will conduct clinical trials in pediatric cancers including medulloblastoma, retinoblastoma and pediatric sarcomas and in rectal cancer and choroidal melanoma. We hypothesize that proton therapy will produce fewer acute and late effects in developing children, e.g., growth defects, cognitive changes, organ damage and secondary tumors, than those resulting from photon beam treatment. In medulloblastoma and rectal cancer, we will investigate whether the reduced treatment volumes resulting from proton beams will decrease co-morbidity in multi-modality treatments and whether patient-reported QOL is improved. We will investigate whether altered fractionation decreases the loss of visual acuity in patients treated for choroidal melanoma compared to that found in standard proton treatments. New areas of focus in this application are inclusion of chemotherapy in those sites where it has become standard treatment, and QOL studies to assess the total range of benefits resulting from improved dose distributions. We expect that the highly conformal dose distributions achievable with proton therapy will result in a reduction in treatment-related morbidity and improved QOL. A reduction in acute morbidity in combined modality treatment may improve treatment intensity and compliance which could ultimately impact on cancer control.